Vitamin D deficiency may limit immune recovery in HIV-positive adults

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The level of HIV-1 in the blood of an HIV-infected partner is the single most important factor influencing risk of sexual transmission to an uninfected partner, according to a multinational study of heterosexual couples in sub-Saharan Africa. The study, published in the Journal of Infectious Diseases, calculated the risk of HIV-1 transmission per act of sexual intercourse and found the average rate of infection to be about 1 per 900 coital acts. The findings also confirmed that condoms are highly protective and reduce HIV infectivity by 78 percent. James P. Hughes, PhD, and colleagues at the University of Washington and the Fred Hutchinson Cancer Research Center, in Seattle; the University of Witwatersrand in South Africa; the University of Nairobi and Kenyatta National Hospital, in Kenya; and the Rwanda-Zambia HIV Research Group conducted a study that included 3,297 HIV-discordant couples (where one person is HIV-infected, and the other is not) in eastern and southern Africa who were enrolled in a randomized trial of acyclovir suppressive therapy. The couples had frequent follow-up to measure plasma HIV-1 RNA in the infected partner and genetic testing to link the transmitted virus to the index HIV-infected partner, to prevent inclusion of infections acquired from other possible partners. HIV acquisition was not affected by the acyclovir therapy. The study confirmed that condoms are highly protective, reducing the risk of HIV transmission by 78 percent when subjects reported using a condom. Most important, the authors noted, was the level of HIV-1 RNA in the blood of the infected partner. The higher the viral load in the index infected partner, the higher the risk of transmission, emphasizing the importance of lowering viral load to help prevent the spread of HIV-1 through sex. Older age was associated with reduced transmission per sex act, and male circumcision reduced female-to-male transmission by approximately 47 percent. Genital herpes infections and the presence of genital ulcers were associated with increased rates of transmission. "Our results underscore the importance of antiretroviral therapy, and, possibly, treatment of co-infections, to reduce plasma HIV-1 viral load in HIV-1 infected partners, and condom promotion, male circumcision, and treatment of symptomatic sexually-transmitted infections for HIV-1 uninfected partners as potential interventions to reduce HIV-1 transmission," the authors wrote. The findings also showed that the risk of an HIV-infected man transmitting an infection to a woman not infected with HIV was about twice the risk of an HIV-infected woman transmitting to an HIV-uninfected man. However, this difference can be attributed to the difference in viral loads between men and women, the authors noted. On average, HIV-infected men have higher HIV-1 loads. Difference in age and having genital herpes in the HIV-uninfected partners also help account for the disparity—the HIV-uninfected female partners were, on average, younger and had higher rates of genital herpes than their male counterparts. Previous studies examining HIV-1 per-act infectivity have been significantly smaller and not as comprehensive in terms of measuring plasma HIV-1 RNA and the use of genetic linkage of transmissions. In an editorial commentary, Ronald H. Gray, MD, and Maria J. Wawer, MD, both of Johns Hopkins University in Baltimore, noted that Dr. Hughes and his colleagues have possibly recorded the most precise estimates of HIV-1 transmission per sexual act during latent HIV disease, providing a valuable addition to knowledge in this area, where much remains to be learned. Additional research using the genetic data collected from this study, in addition to new data from another recently completed clinical trial, is planned to help explain the variation in transmission risk among couples, the authors noted. Fast Facts: 1. In HIV-discordant couples—where one partner is infected with HIV, and the other is not—viral load of the infected partner was a major factor affecting the HIV transmission rate. 2. Condom use among HIV-discordant couples was 78 percent effective in preventing transmission to the uninfected partner. 3. Factors such as age, male circumcision status, and sexually transmitted infections also affected transmission probability

A University of Georgia researcher has found that low levels of vitamin D may limit the effectiveness of HIV treatment in adults.

Those with human immunodeficiency virus—commonly known as HIV—often struggle with declining health because their immune systems can’t effectively respond to common pathogens. Their immune statuses, usually measured by CD4+T cells, normally improve when given HIV treatment.

“Because of the immune-destroying effects of HIV, infection usually results in relatively quick death without treatment. The magic of antiretroviral therapy, the name for drugs to treat HIV, lies in its ability to restore immune function,” said study co-author Amara Ezeamama, an assistant professor of epidemiology and biostatistics in the College of Public Health.

“With antiretroviral drugs, people with HIV are beginning to live longer lives. Our goal was to understand whether vitamin D deficiency limits the amount of immune recovery benefit for persons on HIV treatment.”

The findings were published recently in the journal Clinical Nutrition.

Ezeamama conducted an 18-month longitudinal study in which the immune status of 398 HIV-positive adults was measured at 0, 3, 6, 12 and 18 months. The researchers, through observation, related the rise in immune function to whether or not individuals had adequate levels of vitamin D.

Specifically, Ezeamama found that vitamin D helped the adults’ CD4+T cells recover more quickly. CD4+T cells are a type of T cell that helps the immune system fight off pathogens. For HIV-positive adults, CD4+T cells are critical because of their weakened immune systems.

Ezeamama found that participants with sufficient levels of vitamin D recovered more of their immune function—on average 65 CD4+T cells more—than those with vitamin D deficiency. The benefit of vitamin D sufficiency seemed greater for younger and underweight HIV-positive adults.

“HIV destroys the capacity of the body to mount effective response to pathogens,” Ezeamama said. “Given different vitamin D levels, HIV-positive adults recovered at different rates. We found a relationship between vitamin D and CD4+T cells.”

During the study, the participants were observed while on highly active antiretroviral therapy, or HAART, which normally consists of three or more drugs and is currently the most common—and most effective—treatment for HIV-positive adults. Those on HAART take it daily.

“It’s a cocktail of several medicines that controls the virus,” Ezeamama explained. “In addition to HAART, ensuring vitamin D sufficiency may also be helpful in restoring immune function.

“As researchers, we want to know what we can do to help. Vitamin D is relatively cheap. If we intervene with it, it could give individual HIV-infected persons a modest immune recovery bump that will likely translate to big public health impact.”

In the future, Ezeamama wants to look at how vitamin D affects immune recovery and long-term health outcomes in HIV-positive children.

“We are now in an era of hope for persons with HIV,” she said. “We know that HIV treatment works, and now people can live for several decades with HIV. We can further delay the progress of the disease and maintain survivors on a higher quality of life if we understand the factors that limit the effectiveness of HIV treatment.”

Study co-authors include David Guwatudde and Rachel Kyunene of Makerere University College of Health Sciences; Molin Wang, Wafaie W. Fawzi and Christopher Sudfeld of the Harvard University School of Public Health; Danstan Bagenda of Makerere University College of Health Sciences and Harvard School of Public Health; and Yukari C. Manabe of Makerere University College of Health Sciences and John Hopkins University.

The study, “Vitamin-D deficiency impairs CD4+T-cell count recovery rate in HIV-positive adults on highly active antiretroviral therapy: A longitudinal study,” is available atwww.sciencedirect.com/science/article/pii/S0261561415002289. The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award number R01HD060333.


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